CN111925385B - 硼的酯和酸化合物的合成 - Google Patents
硼的酯和酸化合物的合成 Download PDFInfo
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- CN111925385B CN111925385B CN202010514035.2A CN202010514035A CN111925385B CN 111925385 B CN111925385 B CN 111925385B CN 202010514035 A CN202010514035 A CN 202010514035A CN 111925385 B CN111925385 B CN 111925385B
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 213
- 239000002253 acid Chemical class 0.000 title claims abstract description 64
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 title abstract description 31
- 229910052796 boron Inorganic materials 0.000 title abstract description 18
- 150000002148 esters Chemical class 0.000 title abstract description 17
- 238000003786 synthesis reaction Methods 0.000 title abstract description 12
- 230000015572 biosynthetic process Effects 0.000 title abstract description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 204
- 238000000034 method Methods 0.000 claims description 162
- -1 borate compound Chemical class 0.000 claims description 144
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 141
- 239000002904 solvent Substances 0.000 claims description 120
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 116
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 116
- 239000000203 mixture Substances 0.000 claims description 106
- 125000003118 aryl group Chemical group 0.000 claims description 93
- 238000006243 chemical reaction Methods 0.000 claims description 88
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 claims description 78
- 239000011541 reaction mixture Substances 0.000 claims description 75
- 125000001931 aliphatic group Chemical group 0.000 claims description 64
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 61
- 230000008569 process Effects 0.000 claims description 61
- 238000005859 coupling reaction Methods 0.000 claims description 44
- 230000008878 coupling Effects 0.000 claims description 42
- 238000010168 coupling process Methods 0.000 claims description 42
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 42
- 239000002841 Lewis acid Substances 0.000 claims description 41
- 150000007517 lewis acids Chemical class 0.000 claims description 41
- 238000003756 stirring Methods 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 33
- 239000003153 chemical reaction reagent Substances 0.000 claims description 31
- 125000006239 protecting group Chemical group 0.000 claims description 31
- 239000003960 organic solvent Substances 0.000 claims description 28
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 21
- 238000002360 preparation method Methods 0.000 claims description 20
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 20
- 239000012455 biphasic mixture Substances 0.000 claims description 19
- 239000004327 boric acid Substances 0.000 claims description 18
- 229910052783 alkali metal Inorganic materials 0.000 claims description 17
- 150000008064 anhydrides Chemical class 0.000 claims description 16
- 150000001340 alkali metals Chemical class 0.000 claims description 15
- 238000010511 deprotection reaction Methods 0.000 claims description 15
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 14
- 239000002250 absorbent Substances 0.000 claims description 13
- 230000002745 absorbent Effects 0.000 claims description 13
- 125000005620 boronic acid group Chemical group 0.000 claims description 13
- 239000000460 chlorine Substances 0.000 claims description 12
- 238000002425 crystallisation Methods 0.000 claims description 12
- 230000008025 crystallization Effects 0.000 claims description 12
- 125000004122 cyclic group Chemical group 0.000 claims description 12
- 150000003512 tertiary amines Chemical class 0.000 claims description 12
- 238000005406 washing Methods 0.000 claims description 12
- 239000004215 Carbon black (E152) Substances 0.000 claims description 11
- 229910052801 chlorine Inorganic materials 0.000 claims description 11
- 229930195733 hydrocarbon Natural products 0.000 claims description 11
- 150000002430 hydrocarbons Chemical class 0.000 claims description 11
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
- NIPZZXUFJPQHNH-UHFFFAOYSA-N pyrazine-2-carboxylic acid Chemical compound OC(=O)C1=CN=CC=N1 NIPZZXUFJPQHNH-UHFFFAOYSA-N 0.000 claims description 6
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 5
- 239000011707 mineral Substances 0.000 claims description 5
- 239000007858 starting material Substances 0.000 claims description 5
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 4
- 239000012317 TBTU Substances 0.000 claims 1
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 abstract description 15
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 abstract description 13
- 229960001467 bortezomib Drugs 0.000 abstract description 13
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 4
- 229940079156 Proteasome inhibitor Drugs 0.000 abstract description 3
- 239000003207 proteasome inhibitor Substances 0.000 abstract description 3
- 238000010189 synthetic method Methods 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 89
- 239000010410 layer Substances 0.000 description 70
- 125000001072 heteroaryl group Chemical group 0.000 description 57
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 35
- JKWMSGQKBLHBQQ-UHFFFAOYSA-N diboron trioxide Chemical compound O=BOB=O JKWMSGQKBLHBQQ-UHFFFAOYSA-N 0.000 description 33
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 32
- 229910052760 oxygen Inorganic materials 0.000 description 32
- 239000001301 oxygen Substances 0.000 description 32
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 29
- 229910052757 nitrogen Inorganic materials 0.000 description 28
- 239000000047 product Substances 0.000 description 27
- 125000004432 carbon atom Chemical group C* 0.000 description 24
- 239000006184 cosolvent Substances 0.000 description 24
- 239000001257 hydrogen Substances 0.000 description 23
- 229910052739 hydrogen Inorganic materials 0.000 description 23
- 239000007787 solid Substances 0.000 description 23
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 20
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 20
- 229910052717 sulfur Inorganic materials 0.000 description 20
- 125000000217 alkyl group Chemical group 0.000 description 19
- 239000000126 substance Substances 0.000 description 19
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 18
- 239000011521 glass Substances 0.000 description 18
- 125000005842 heteroatom Chemical group 0.000 description 18
- 239000011593 sulfur Substances 0.000 description 17
- 239000002585 base Substances 0.000 description 16
- 229910052799 carbon Inorganic materials 0.000 description 16
- 239000008367 deionised water Substances 0.000 description 16
- 229910021641 deionized water Inorganic materials 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 125000000623 heterocyclic group Chemical group 0.000 description 15
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 239000012071 phase Substances 0.000 description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 14
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 13
- 125000003710 aryl alkyl group Chemical group 0.000 description 13
- 238000004519 manufacturing process Methods 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000008346 aqueous phase Substances 0.000 description 12
- 230000000903 blocking effect Effects 0.000 description 12
- 150000001642 boronic acid derivatives Chemical class 0.000 description 12
- 150000001721 carbon Chemical group 0.000 description 12
- 238000001914 filtration Methods 0.000 description 12
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 11
- 238000001035 drying Methods 0.000 description 11
- 238000004817 gas chromatography Methods 0.000 description 11
- 230000014759 maintenance of location Effects 0.000 description 11
- 230000002829 reductive effect Effects 0.000 description 11
- 238000004007 reversed phase HPLC Methods 0.000 description 11
- 125000001424 substituent group Chemical group 0.000 description 11
- XHDGJGJBAQDXON-VYDKEIKOSA-N (4s,5r)-4,6,6-trimethylbicyclo[3.1.1]heptane-4,5-diol Chemical compound C1[C@@]2(O)C(C)(C)C1CC[C@@]2(O)C XHDGJGJBAQDXON-VYDKEIKOSA-N 0.000 description 10
- 229940126214 compound 3 Drugs 0.000 description 10
- 239000012535 impurity Substances 0.000 description 10
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 10
- 239000012299 nitrogen atmosphere Substances 0.000 description 10
- 230000008707 rearrangement Effects 0.000 description 10
- 239000006227 byproduct Substances 0.000 description 9
- 150000001768 cations Chemical class 0.000 description 9
- 229940125904 compound 1 Drugs 0.000 description 9
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 9
- 125000001309 chloro group Chemical group Cl* 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 238000002156 mixing Methods 0.000 description 8
- MOILFCKRQFQVFS-VUMZSGCYSA-N (3r,4s)-4,6,6-trimethylbicyclo[3.1.1]heptane-3,4-diol Chemical compound C1C2C(C)(C)C1C[C@@H](O)[C@]2(O)C MOILFCKRQFQVFS-VUMZSGCYSA-N 0.000 description 7
- 125000003342 alkenyl group Chemical group 0.000 description 7
- 229940024606 amino acid Drugs 0.000 description 7
- 150000001413 amino acids Chemical class 0.000 description 7
- 229910052736 halogen Inorganic materials 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 239000011592 zinc chloride Substances 0.000 description 7
- 235000005074 zinc chloride Nutrition 0.000 description 7
- 238000006219 Matteson homologation reaction Methods 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- 125000002252 acyl group Chemical group 0.000 description 6
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 6
- 125000000753 cycloalkyl group Chemical group 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000003517 fume Substances 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- 238000002955 isolation Methods 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 6
- 239000004743 Polypropylene Substances 0.000 description 5
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- 239000012043 crude product Substances 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
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- 239000011734 sodium Substances 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- 125000000304 alkynyl group Chemical group 0.000 description 4
- OWBTYPJTUOEWEK-UHFFFAOYSA-N butane-2,3-diol Chemical compound CC(O)C(C)O OWBTYPJTUOEWEK-UHFFFAOYSA-N 0.000 description 4
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- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
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- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 description 4
- RQJMOCIAILRHIC-JUUVMNCLSA-N (2s)-2-amino-4-methylpentanoic acid;(2s)-2-amino-3-phenylpropanoic acid Chemical compound CC(C)C[C@H](N)C(O)=O.OC(=O)[C@@H](N)CC1=CC=CC=C1 RQJMOCIAILRHIC-JUUVMNCLSA-N 0.000 description 3
- ZAZPDOYUCVFPOI-UHFFFAOYSA-N 2-methylpropylboronic acid Chemical group CC(C)CB(O)O ZAZPDOYUCVFPOI-UHFFFAOYSA-N 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
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- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
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- 125000004429 atom Chemical group 0.000 description 3
- 125000002837 carbocyclic group Chemical group 0.000 description 3
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- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 3
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- FEONEKOZSGPOFN-UHFFFAOYSA-K tribromoiron Chemical compound Br[Fe](Br)Br FEONEKOZSGPOFN-UHFFFAOYSA-K 0.000 description 1
- 230000006663 ubiquitin-proteasome pathway Effects 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000004078 waterproofing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/04—Esters of boric acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Virology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Transplantation (AREA)
- Tropical Medicine & Parasitology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- AIDS & HIV (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US55753504P | 2004-03-30 | 2004-03-30 | |
| US60/557,535 | 2004-03-30 | ||
| PCT/US2005/009774 WO2005097809A2 (fr) | 2004-03-30 | 2005-03-24 | Synthese d'ester borique et de composes acides |
| CN200580017645.5A CN1960996B (zh) | 2004-03-30 | 2005-03-24 | 硼的酯和酸化合物的合成 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200580017645.5A Division CN1960996B (zh) | 2004-03-30 | 2005-03-24 | 硼的酯和酸化合物的合成 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111925385A CN111925385A (zh) | 2020-11-13 |
| CN111925385B true CN111925385B (zh) | 2023-11-21 |
Family
ID=34968044
Family Applications (5)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010514035.2A Active CN111925385B (zh) | 2004-03-30 | 2005-03-24 | 硼的酯和酸化合物的合成 |
| CN201710810795.6A Pending CN107474062A (zh) | 2004-03-30 | 2005-03-24 | 硼的酯和酸化合物的合成 |
| CN200580017645.5A Active CN1960996B (zh) | 2004-03-30 | 2005-03-24 | 硼的酯和酸化合物的合成 |
| CN201810192292.1A Active CN108329337B (zh) | 2004-03-30 | 2005-03-24 | 硼的酯和酸化合物的合成 |
| CN201310294873.3A Active CN103396427B (zh) | 2004-03-30 | 2005-03-24 | 硼的酯和酸化合物的合成 |
Family Applications After (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710810795.6A Pending CN107474062A (zh) | 2004-03-30 | 2005-03-24 | 硼的酯和酸化合物的合成 |
| CN200580017645.5A Active CN1960996B (zh) | 2004-03-30 | 2005-03-24 | 硼的酯和酸化合物的合成 |
| CN201810192292.1A Active CN108329337B (zh) | 2004-03-30 | 2005-03-24 | 硼的酯和酸化合物的合成 |
| CN201310294873.3A Active CN103396427B (zh) | 2004-03-30 | 2005-03-24 | 硼的酯和酸化合物的合成 |
Country Status (41)
| Country | Link |
|---|---|
| US (14) | US7714159B2 (fr) |
| EP (5) | EP2377868A1 (fr) |
| JP (4) | JP4558039B2 (fr) |
| KR (1) | KR100939598B1 (fr) |
| CN (5) | CN111925385B (fr) |
| AR (3) | AR049374A1 (fr) |
| AT (1) | ATE521612T1 (fr) |
| AU (1) | AU2005230930B2 (fr) |
| BR (1) | BRPI0509587A (fr) |
| CA (4) | CA2853272A1 (fr) |
| CL (2) | CL2010000350A1 (fr) |
| CR (1) | CR8653A (fr) |
| CY (3) | CY1112053T1 (fr) |
| DK (4) | DK1756121T3 (fr) |
| DO (1) | DOP2011000293A (fr) |
| EA (1) | EA012927B1 (fr) |
| EC (1) | ECSP066960A (fr) |
| ES (3) | ES2457593T3 (fr) |
| FI (1) | FI4008721T3 (fr) |
| HK (4) | HK1100004A1 (fr) |
| HR (4) | HRP20212002T1 (fr) |
| HU (1) | HUE056859T2 (fr) |
| IL (3) | IL178250A (fr) |
| LT (2) | LT4008721T (fr) |
| ME (1) | ME01975B (fr) |
| MX (1) | MX367324B (fr) |
| MY (1) | MY145427A (fr) |
| NL (3) | NL1028639C2 (fr) |
| NO (4) | NO338905B1 (fr) |
| NZ (3) | NZ550522A (fr) |
| PE (3) | PE20110075A1 (fr) |
| PL (4) | PL4008721T3 (fr) |
| PT (4) | PT1756121E (fr) |
| RS (4) | RS65253B1 (fr) |
| SG (5) | SG182999A1 (fr) |
| SI (4) | SI3385267T1 (fr) |
| TW (1) | TWI386212B (fr) |
| UA (1) | UA90108C2 (fr) |
| UY (3) | UY28830A1 (fr) |
| WO (1) | WO2005097809A2 (fr) |
| ZA (1) | ZA200608689B (fr) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6083903A (en) * | 1994-10-28 | 2000-07-04 | Leukosite, Inc. | Boronic ester and acid compounds, synthesis and uses |
| DK1756121T3 (da) | 2004-03-30 | 2012-01-09 | Millennium Pharm Inc | Syntese af borester- og borsyreforbindelser |
| WO2008075376A1 (fr) * | 2006-12-18 | 2008-06-26 | Natco Pharma Limited | Formes polymorphes du bortézomibe et leur procédé de préparation |
| WO2009004350A1 (fr) * | 2007-07-03 | 2009-01-08 | Pliva Hrvatska D.O.O. | Procédé de préparation du bortézomib et intermédiaires utilisés dans sa préparation |
| EA034601B1 (ru) * | 2007-08-06 | 2020-02-25 | Милленниум Фармасьютикалз, Инк. | Способ получения бороновых кислот |
| US7442830B1 (en) | 2007-08-06 | 2008-10-28 | Millenium Pharmaceuticals, Inc. | Proteasome inhibitors |
| AU2016253697A1 (en) * | 2007-08-06 | 2016-11-24 | Millennium Pharmaceuticals, Inc. | Proteasome inhibitors |
| KR20140042933A (ko) | 2007-08-06 | 2014-04-07 | 밀레니엄 파머슈티컬스 인코퍼레이티드 | 프로테아좀 억제제 |
| WO2009026579A1 (fr) * | 2007-08-23 | 2009-02-26 | Cornell Research Foundation, Inc. | Inhibiteurs de protéasome et leur utilisation dans le traitement d'une affection pathogène et du cancer |
| BRPI0816807A2 (pt) * | 2007-09-12 | 2017-05-16 | Dr Reddy's Laboratories Inc | bortezomib e processo para a produção do mesmo |
| US7838673B2 (en) | 2007-10-16 | 2010-11-23 | Millennium Pharmaceuticals, Inc. | Proteasome inhibitors |
| CA2921946C (fr) | 2008-06-17 | 2019-01-08 | Millennium Pharmaceuticals, Inc. | Composes de borates esters et compositions pharmaceutiques contenant des composes |
| AU2013204881A1 (en) * | 2008-09-29 | 2013-05-16 | Millennium Pharmaceuticals, Inc. | Derivatives of 1-amino-2-cyclobutylethylboronic acid |
| AR075090A1 (es) | 2008-09-29 | 2011-03-09 | Millennium Pharm Inc | Derivados de acido 1-amino-2-ciclobutiletilboronico inhibidores de proteosoma,utiles como agentes anticancerigenos, y composiciones farmaceuticas que los comprenden. |
| EP2238973A1 (fr) | 2009-04-07 | 2010-10-13 | Cephalon France | Préparations lyophilisées d'inhibiteurs du protéasome |
| CN101899062B (zh) * | 2009-05-26 | 2015-04-15 | 上海威智医药科技有限公司 | α-手性硼酸及硼酸酯的合成工艺 |
| EP2280016A1 (fr) | 2009-07-27 | 2011-02-02 | LEK Pharmaceuticals d.d. | Nouvelle voie de synthèse pour la préparation d'esters boroniques aminés via des Alk-1-ynes substitués |
| EP2270019A1 (fr) | 2009-06-19 | 2011-01-05 | LEK Pharmaceuticals d.d. | Nouvelle voie de synthèse pour la préparation d'esters boronique alpha-aminé |
| EP2443128B1 (fr) * | 2009-06-19 | 2017-12-20 | LEK Pharmaceuticals d.d. | Nouvelle voie de synthèse pour la préparation d'esters boronique alpha-aminé |
| EP2516449A1 (fr) | 2009-12-22 | 2012-10-31 | Cephalon, Inc. | Inhibiteurs du protéasome et leurs procédés de préparation, d'épuration et d'utilisation |
| WO2011090940A1 (fr) | 2010-01-19 | 2011-07-28 | Cerulean Pharma Inc. | Polymères à base de cyclodextrine pour administration thérapeutique |
| AU2011214024A1 (en) | 2010-02-09 | 2012-08-30 | Ranbaxy Laboratories Limited | Process for the preparation of bortezomib |
| CN101781326B (zh) * | 2010-02-11 | 2013-08-21 | 福建南方制药股份有限公司 | 一种制备手性氨基硼酸的中间体及其制备方法 |
| WO2011107912A1 (fr) | 2010-03-04 | 2011-09-09 | Ranbaxy Laboratories Limited | Formes polymorphes de bortézomib |
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| CN101812026B (zh) * | 2010-04-12 | 2013-08-28 | 亚邦医药股份有限公司 | 一种硼替佐米的合成方法 |
| EA035193B1 (ru) | 2010-05-18 | 2020-05-14 | Серулин Фарма Инк. | Композиции и способы лечения аутоиммунных и других заболеваний |
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| US8497374B2 (en) | 2011-05-12 | 2013-07-30 | Scinopharm Taiwan, Ltd. | Process for preparing and purifying bortezomib |
| CN102268029B (zh) * | 2011-05-19 | 2013-10-09 | 苏州二叶制药有限公司 | 化合物（1s,2s,3r,5s）-蒎烷二醇-l-苯丙氨酸-l-亮氨酸硼酸酯的制备 |
| CA2833775A1 (fr) | 2011-06-22 | 2012-12-27 | Cephalon, Inc. | Inhibiteurs du proteasome et leurs methodes de preparation, de purification et d'utilisation |
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| CN103897027A (zh) * | 2012-12-29 | 2014-07-02 | 曹亚英 | 关键中间体晶型，制备方法及其在硼替佐米合成中的运用 |
| WO2014110442A1 (fr) | 2013-01-10 | 2014-07-17 | VenatoRx Pharmaceuticals, Inc. | Inhibiteurs de bêta-lactamase |
| EP2986619A1 (fr) | 2013-04-16 | 2016-02-24 | Cipla Limited | Procédé pour la préparation d'ester de mannitol du bortézomib |
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| CN103497233B (zh) * | 2013-09-30 | 2015-04-08 | 哈药集团技术中心 | 一种硼替佐米的制备方法 |
| CN103554219A (zh) * | 2013-10-01 | 2014-02-05 | 昆明贵研药业有限公司 | 一种制备硼替佐米的方法 |
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| US10167311B2 (en) | 2014-02-03 | 2019-01-01 | Ohio State Innovation Foundation | Boronic acid esters and pharmaceutical formulations thereof |
| BR112016026774A8 (pt) | 2014-05-20 | 2021-07-13 | Millennium Pharm Inc | uso de inibidores de proteassoma contendo boro após terapia de câncer primária e composição farmacêutica. |
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| WO2002059130A1 (fr) * | 2001-01-25 | 2002-08-01 | The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Formulation de composes d'acide boronique |
| JPWO2003033507A1 (ja) * | 2001-10-12 | 2005-02-03 | 杏林製薬株式会社 | ベンジルマロン酸誘導体およびそれを含有するプロテアソーム阻害薬 |
| JPWO2003033506A1 (ja) * | 2001-10-12 | 2005-02-03 | 杏林製薬株式会社 | アミノボラン酸誘導体およびそれを含有するプロテアソーム阻害薬 |
| DK1756121T3 (da) | 2004-03-30 | 2012-01-09 | Millennium Pharm Inc | Syntese af borester- og borsyreforbindelser |
| WO2009004350A1 (fr) * | 2007-07-03 | 2009-01-08 | Pliva Hrvatska D.O.O. | Procédé de préparation du bortézomib et intermédiaires utilisés dans sa préparation |
| US7838673B2 (en) * | 2007-10-16 | 2010-11-23 | Millennium Pharmaceuticals, Inc. | Proteasome inhibitors |
| EP2443128B1 (fr) * | 2009-06-19 | 2017-12-20 | LEK Pharmaceuticals d.d. | Nouvelle voie de synthèse pour la préparation d'esters boronique alpha-aminé |
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